Synthesis and antiviral activity of novel glycyrrhizic acid conjugates with D-amino acid esters

Fayrushina, A. I.; Балтина, Л. А.; Коновалова, Н. И.; Petrova, P. A.; Eropkin, M. Yu.

doi:10.1134/s1068162017040045

Cited by 12 publications

(11 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main component of Glycyrrhizae Radix , glycyrrhizin, may protect mice exposed to a lethal amount of influenza virus through the stimulation of IFN- γ production by T cells and has been reported to inhibit influenza A virus uptake into the cell [ 17 ]. Glycyrrhizin concentrations that inhibited H5N1-induced proinflammatory gene expression did not affect natural killer cells' cytolytic activity [ 18 ]. Furthermore, emodin, an active component of Polygoni Cuspidati Rhizoma , inhibits the replication of influenza virus H1N1 in A549 cells [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus

Chen

Zhou

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

Background. Traditional Chinese medicine Yinhuapinggan granule (YHPG) has been used for treating upper respiratory tract infection like influenza, cough, and viral pneumonia. However, its active ingredients that really exert the main efficacy have not been well elucidated. This study is aimed at screening its antiviral components and investigating the potential therapeutic mechanisms of YHPG against the influenza A/PR8/34 (H1N1) virus in Madin Darby canine kidney (MDCK). Methods. MDCK cells were infected with the influenza virus and then treated with ribavirin, YHPG, and main active ingredients in YHPG. Based on the maximum nontoxic concentration (TC0), half-maximal toxic concentration (TC50), half-maximal inhibitory concentration (IC50), and therapeutic index (TI), interferon-β (IFN-β) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the gene expression of TLR7, MyD88, tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Jun amino terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and p65 nuclear transcription factor-kappa B (p65 NF-κB) was quantified using reverse transcription-polymerase chain reaction (RT-PCR). Results. The results indicated that the components of YHPG, such as ephedrine hydrochloride, pseudoephedrine hydrochloride, chlorogenic acid, and emodin, had significant antiviral effects. High and medium doses of YHPG effectively reduced the cytopathic effect (CPE) and significantly decreased IFN-β and IL-6 levels in the supernatant. Simultaneously, the transcript levels of TLR7, MyD88, TRAF6, JNK, p38 MAPK, and p65 NF-κB decreased in infected MDCK cells. Moreover, a certain dose-dependent relationship among different groups of YHPG was observed. Conclusions. These results indicated that YHPG and the components of YHPG had a significant inhibitory function on the proliferation of the H1N1 virus. The mechanism might be associated with suppressing the activation of the TLR7/MyD88 signaling pathway, a decrease in the mRNA expression of key target genes, and inhibition of IFN-β and IL-6 secretion.

show abstract

Section: Discussionmentioning

confidence: 99%

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus

Chen

Zhou

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…We synthesized a series of GL derivatives, which exceed the natural glycoside by anti-HIV activity [ 32 , 39 ]. The inhibitory effect was found for GL derivatives in vitro against the SARS-associated coronaviruses [ 40 ], Epstein-Barr virus [ 41 ], and influenza A/H1N1 virus [ 42 , 43 ]. GL inhibits several pathogenic flaviviruses such as yellow fever virus and DENV at high non-toxic concentrations [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

Hour

Chen

Lin

et al. 2022

IJMS

View full text Add to dashboard Cite

Dengue virus (DENV) is one of the most geographically distributed mosquito-borne flaviviruses, like Japanese encephalitis virus (JEV), and Zika virus (ZIKV). In this study, a library of the known and novel Glycyrrhizic acid (GL) derivatives bearing amino acid residues or their methyl/ethyl esters in the carbohydrate part were synthesized and studied as DENV inhibitors in vitro using the cytopathic effect (CPE), viral infectivity and virus yield assays with DENV1 and DENV-2 in Vero E6 and A549 cells. Among the GL conjugates tested, compound hits GL-D-ValOMe 3, GL-TyrOMe 6, GL-PheOEt 11, and GL-LysOMe 21 were discovered to have better antiviral activity than GL, with IC50 values ranging from <0.1 to 5.98 μM on the in vitro infectivity of DENV1 and DENV2 in Vero E6 and A549 cells. Compound hits 3, 6, 11, and 21 had a concentration-dependent inhibition on the virus yield in Vero E6, in which GL-D-ValOMe 3 and GL-PheOEt 11 were the most active inhibitors of DENV2 yield. Meanwhile, the time-of-addition assay indicated that conjugates GL-D-ValOMe 3 and GL-PheOEt 11 exhibited a substantial decrease in the DENV2 attachment stage. Subsequently, chimeric single-round infectious particles (SRIPs) of DENV2 C-prM-E protein/JEV replicon and DENV2 prM-E/ZIKV replicon were utilized for the DENV envelope I protein-mediated attachment assay. GL conjugates 3 and 11 significantly reduced the attachment of chimeric DENV2 C-prM-E/JEV and DENV2 prM-E/ZIKV SRIPs onto Vero E6 cells in a concentration-dependent manner but did not impede the attachment of wild-type JEV CprME/JEV and ZIKV prM-E/ZIKV SRIPs, indicating the inhibition of Compounds 3 and 11 on DENV2 E-mediated attachment. Molecular docking data revealed that Compounds 3 and 11 have hydrophobic interactions within a hydrophobic pocket among the interfaces of Domains I, II, and the stem region of the DENV2 envelope (E) protein. These results displayed that Compounds 3 and 11 were the lead compounds targeting the DENV E protein. Altogether, our findings provide new insights into the structure–activity relationship of GL derivatives conjugated with amino acid residues and can be the new fundamental basis for the search and development of novel flavivirus inhibitors based on natural compounds.

show abstract

“…22 Most recently, we detected inhibitory effects of GL derivatives in vitro against influenza A/H1N1 virus. 23,24 GL is also of interest as a scaffold for the preparation of potential inhibitors of pathogenic flaviviruses like DENV, since it is reported about the GL ability to inhibit DENV and yellow fever viruses at high non-toxic concentrations. 25 .…”

mentioning

confidence: 99%

“…[29][30][31] GL conjugates (10)(11)(12), containing D-amino acids methyl esters, were synthesized according to Ref. 24 , conjugates (13)(14) with free amino acids according to Refs. 32,33 .…”

mentioning

confidence: 99%

Glycyrrhizic acid derivatives as Dengue virus inhibitors

Baltina

Tasi

Huang

et al. 2019

Bioorganic & Medicinal Chemistry Letters

View full text Add to dashboard Cite

Synthesis and antiviral activity of novel glycyrrhizic acid conjugates with D-amino acid esters

Cited by 12 publications

References 12 publications

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

Glycyrrhizic acid derivatives as Dengue virus inhibitors

Contact Info

Product

Resources

About